Hereditary complement (C) deficiency states in man form a major basis for this research. These genetic deficiencies are being evaluated in their own right (a) in order to elucidate the associations with infectious, rheumatic or immunologic diseases; (b) to determine linkages to many known genetic markers. In addition, various C-deficient sera are being utilized to extend knowledge on the biological role of C in host defense mechanisms and cellular injury in man, including studies of the nature of C-dependent chemotactic factors, serum opsonic activity for bacteria and yeasts, intracellular killing of bacteria, neutralization of enveloped viruses, C-dependent platelet aggregation and release reactions, and the ultrastructural basis of C injury to cell membranes.